Individual models for virtual bone drilling in mastoid surgery.

Segmented training cases for virtual simulation of bone-drilling interventions in middle ear surgery have proven to be helpful in learning about surgical anatomy of the temporal bone. The anatomy of the mastoid shows a high degree of variability, however, and the aim of this study was to evaluate whether individual virtual models could be created within an affordable timeframe, and to what extend they reflected natural individual anatomy during virtual mastoid surgery. Automatic segmentation schemes were used, and these reduced the time required to create individual models on the basis of DICOM CT scans to less than 5 minutes. Models based on CT data with a slice distance of 0.4 mm or better were found to provide excellent handling, an acceptable depiction of mastoidal organs, and a helpful impression of the individual surgical situation. Although landmarks are still more easily detected in real mastoids, virtual drilling of individual models makes the 3D estimation of specific anatomy more effective than estimations based on interpretation of CT scans alone.

Interleukin-13 acts as an apoptotic effector on lung epithelial cells and induces pro-fibrotic gene expression in lung fibroblasts.

BACKGROUND: IL-13 promotes acute allergic asthma and is discussed to play a role in late asthmatic features such as fibrotic processes and airway remodelling. The contributions of IL-13-mediated mechanisms to subepithelial events related to fibrosis are not yet settled. OBJECTIVE: We investigated the impact of IL-13 on lung epithelial cells as apoptotic effector and on lung fibroblasts as inducer of pro-fibrotic gene expression. METHODS: Using the two lung epithelial cell lines A549 and BEAS-2B as well as primary lung epithelial cells, we investigated the capability of IL-13 to induce apoptosis by both flow-cytometry and ELISA. The ability of IL-13 to increase the expression of pro-fibrotic genes and to exert influence on the expression of its own receptor was investigated by real-time quantitative PCR measurement of mRNAs encoding collagen I, collagen III, basic fibroblast growth factor (bFGF), alpha-smooth muscle actin (alpha-SMA) and the IL-13 receptor alpha1 (IL-13Ralpha1) chain in human primary lung fibroblasts. The specificity of IL-13-mediated cellular responses was confirmed by means of an inhibitory monoclonal antibody directed to the IL-13 receptor. RESULTS: IL-13 induces apoptosis in lung epithelial cell lines as well as in primary lung epithelial cells. Furthermore, IL-13 increases the expression of mRNA for alpha-SMA and collagen III, but not for bFGF in human primary lung fibroblasts. The susceptibility of lung fibroblasts to IL-13-induced up-regulation of pro-fibrotic genes is associated with the regulation of IL-13 receptor expression. IL-13-dependent fibrosis-associated effects could be inhibited by antibody-mediated blockade of the IL-13Ralpha1 subunit. CONCLUSION: Our findings indicate a function of IL-13 as a mediator in fibrotic processes leading to loss of functional airway tissue in asthma. They also highlight the therapeutic potential of specifically targeting the interaction between IL-13 and its receptor.

A novel interactive anatomic atlas of the hand.

Classical anatomic atlases cannot provide the spectrum of views and the detail required in modern diagnostic and surgical techniques. Computer modeling opens the possibility to choose any view from one single model. A computerized model of the hand is presented, which has been obtained by segmentation and graphic modeling of the Visible Human dataset. In addition to being able to choose arbitrary viewpoints, it allows interrogation of the chosen views by mouse click. We believe the functions of these new kinds of atlases are superior to the classical ones.

EUS Meets Voxel-Man: three-dimensional anatomic animation of linear-array endoscopic ultrasound images.

Endoscopic ultrasonography (EUS) is a widely used imaging modality in gastroenterology. The development of linear-array endoscopic ultrasound transducers, with facilities for EUS-guided diagnostic and therapeutic procedures, led to increasingly widespread use in different areas of the body. Examiners need to have excellent knowledge of anatomy. Orientation in linear EUS is more difficult and the learning curve is long. In an effort to shorten the training, reducing the risk to the patient and to allow a faster learning of the basic anatomic structures EUS meets VOXEL-MAN, an interactive three-dimensional anatomic simulation program has been developed for linear EUS for the purposes of private and independent study.

[Virtual simulation of dental surgery using a three-dimensional computer model with a force feedback system]. / Virtuelle Simulation dentoalveolärer Eingriffe in einem dreidimensionalen Computermodell mit Kraftrückkopplungssystem.

BACKGROUND: Selective reduction of bone without injuring inner structures is an essential part of surgical techniques, especially during dental surgery. Virtual drilling is possible using a new simulator. The following illustrates simulation of an apicectomy. MATERIAL AND METHODS: Using the VOXEL-MAN system, a virtual three-dimensional model of a skull was created based on CT data. Both inferior alveolar nerves and apical inflammations of teeth 23, 25, 36, and 35 were virtually simulated. To achieve a realistic drilling effect with the force feedback system, special tools were integrated into VOXEL-MAN to obtain a high resolution of collision recognition. Adding drilling noises further improved the simulation. Spatial 3D perception was possible with the help of shutter glasses. RESULTS: The presented computer model enabled the visual and haptic observation of complex volume-based models and virtual interaction with them. The haptic feeling proved to be convincing because of collision recognition, consideration of drilling parameters, and addition of drilling noises. Via postoperative reconstructions, polydimensional verification of performed drilling routes is possible. CONCLUSION: Using apicectomies as examples, realistic simulation of dental surgical procedures, even in complex anatomical models, is possible. Generally, it is possible to add virtual pathologies in data sets and/or to use anonymous patient data sets to extend the range of simulated surgical procedures.

Periodic fever (TRAPS) caused by mutations in the TNFalpha receptor 1 (TNFRSF1A) gene of three German patients.

TNF-receptor-associated periodic syndrome (TRAPS) is a recently recognized disorder characterized by prolonged attacks of high fever and severe localized inflammation. TRAPS is caused by dominant mutations in the 55 kDa TNF receptor gene (TNFRSF1A). We here describe three German TRAPS patients of two families with Cys30-->Arg and Thr50-->Met mutations, respectively. Both mutations have already been observed before in other nonrelated families. The Thr50-->Met amino acid exchange, caused by an ACG-->ATG transition, has been reported in two other families of different ethnic background. The possibility that the ACG-->ATG sequence alteration is a mutational hot spot causing TRAPS is discussed. Furthermore, we describe and discuss the symptoms of our patients, possible inducers of febrile attacks, and treatments which the patients had received when their diagnoses were still unknown.

Creating a high-resolution spatial/symbolic model of the inner organs based on the Visible Human.

Computerized three-dimensional models of the human body, based on the Visible Human Project of the National Library of Medicine, so far do not reflect the rich anatomical detail of the original cross-sectional images. In this paper, a spatial/symbolic model of the inner organs is developed, which is based on more than 1000 cryosections and congruent fresh and frozen CT images of the male Visible Human. The spatial description is created using color-space segmentation, graphic modeling, and a matched volume visualization with subvoxel resolution. It is linked to a symbolic knowledge base, providing an ontology of anatomical terms. With over 650 three-dimensional anatomical constituents, this model offers an unsurpassed photorealistic presentation and level of detail. A three-dimensional atlas of anatomy and radiology based on this model is available as a PC-based program.

A realistic model of human structure from the visible human data.

The computer-based 3D models of the human body reported to date suffer from poor spatial resolution. The Visible Human project has delivered high resolution cross-sectional images that are suited for generation of high-quality models. Yet none of the 3D models described to date reflect the quality of the original images. We present a method of segmentation and visualization which provides a new quality of realism and detail. Using the example of a 3D model of the inner organs, we demonstrate that such models, especially when combined with a knowledge base, open new possibilities for scientific, educational, and clinical work.

Exploring the visible human's inner organs with the VOXEL-MAN 3D navigator.

Improved rendering and segmentation techniques lead to a new quality of 3D reconstructions of the Visible Human. Using these we have implemented an interactive atlas of anatomy and radiology of the inner organs.

Planning and rehearsal of surgical interventions in the volume model.

Visualization of 3D medical data is routinely used in a wide range of applications. However, for the planning and rehearsal of surgical interventions more sophisticated techniques for interaction have to be developed. The realistic specification and visualization of free form cuts is needed to allow the 'look and feel' close to a real dissection. The problem here is, since these cuts are not represented by intensity changes, that the gray-level-gradient-method can not be used for the estimation of surface normals. In addition, the interactive repositioning of dissected fragments has to be simulated. We have developed an extended ray-casting algorithm for visualization of object motion in the volume model. We implemented new methods for the representation, modeling and high quality rendering (subvoxel resolution) of arbitrarily shaped cut regions within the volume model. The representation is done using a dynamic data structure. This way, all operations can easily be reversed and the original object information is preserved. The modeling of cut surfaces is done in an independent data volume where the partial-volume-effect, which is the prerequisite for the gray-level-gradient method, is calculated as it would be generated by an imaging system. This way, the localization of cut surfaces at subvoxel resolution and an accurate estimation of the surface normals is achieved. The key point here is to detect if a cut surface really truncates an object or if the object has not been affected by a cutting operation. We will present an new method, called adaptive sampling which allows to determine the situation by the generation of additional sample points (when necessary) during the ray casting process. The described techniques provides the basis for simulation of surgical interventions in the voxel-model which could not be achieved with any surface-based method. We present a system for simulation and rehearsal of otosurgical approaches, where we implemented a drill-like tool with which the student lays off the route to the operating area. The key point is to not injure structures of risk such as the facial nerve. For applications like the simulation of craniofacial surgery we developed a gradual cutting tool ("virtual scalpel").

Exploring the Visible Human using the VOXEL-MAN framework.

In principle the Visible Human data sets are an ideal basis for building electronic atlases. While it is easy to construct such atlases by just offering the possibility of browsing through the 2D slices, constructing realistic 3D models is a huge project. As one rather easy way to establish 3D use, we have registered the Visible Human data to the already existing 3D atlas VOXEL-MAN/brain. This procedure enables one to lookup anatomical detail in an atlas based on radiological images. Concerning the segmentation problem, which is the prerequisite for a real 3D atlas, we have developed an interactive classification method that delivers realistic perspective views of the Visible Human. As these volume based methods require high-end workstations, we finally have developed a multimedia program that runs on standard PCs and uses Quicktime VR movies.

Simulation of cardiac excitation patterns in a three-dimensional anatomical heart atlas.

Computerized anatomical atlas systems enable interactive investigation of digital body models. Here we present a three-dimensional atlas of the human heart, based on image data provided in the Visible Human Project. This heart atlas consists of multiple kinds of cardiac tissues and offers unlimited possibilities for its visual exploration. A temporal dimension is added to the underlying heart model by simulation of cardiac excitation spreading. For this purpose a second generation cellular automata algorithm is adapted to the excitation kinetics of cardiac tissue. The presented system is shown as a successful method for the visualization-based investigation of cardiac excitation.

Interactive volume visualization using "intelligent movies".

High quality visualization of medical volume models as performed by the VOXEL-MAN and similar systems is still too time consuming and the interaction complicated when sophisticated tools like dissection are used. We hence developed a new paradigm allowing to create simpler derivatives of the model, called "intelligent movies". These are in QuickTime or QuickTime VR format which allow interactive exploration with two degrees of freedom. As a decisive novelty, we extended it by a pixelwise link to the knowledge base which may be queried in the image context. Thus scenes emphasizing a selected aspect of the volume model may be created as intelligent movies, which a user (referring physician, student) can explore largely with the functionality of VOXEL-MAN, but in real time--on any standard PC--and also via a JAVA applet within web browsers. This is shown with the example of 3D interactive anatomical atlases and clinical cases.

Partonomies for interactive explorable 3D-models of anatomy.

We introduce a concept to model subtle part-whole-semantics for the use with interactive 3d-models of human anatomy. Similar to experiences with modeling partonomies for physical artifacts like machines or buildings we found one unique part-whole-relation to be insufficient to represent anatomical reality. This claim will be illustrated with anatomical examples. According to the requirements these examples demand, a semantic classification of part-whole-relations is introduced. Initial results in modeling anatomical partonomies for a 3d-visualization environment proved this approach to be an promising way to represent anatomy and to enable powerful complex inferences.

Applications and perspectives in anatomical 3-dimensional modelling of the visible human with VOXEL-MAN.

Up to now computerized interactive 3-dimensional (3D) atlases of human anatomy have been based on radiological data or artificial geometric models as spatial descriptions of morphological structures. Besides the obvious advantages of this data (e.g. already in digital format, geometrical correctness) the lack of high resolution anatomical slices of larger regions of the human body has prevented the use of more realistic anatomical data so far. Now, the Visible Human Project offers high quality anatomical slices of complete cadavers. Therefore, on the one hand, new opportunities for realistic virtual 3D models of anatomy are open. On the other hand, just the major advantages of the visible human data (e.g. realistic colors and textures, high resolution) result in new demands on the image processing and visualization techniques. This paper describes experience, solutions and results with a volume-based approach for building realistic anatomical 3D models.

Segmentation of the visible human for high-quality volume-based visualization.

This article describes a combination of interactive classification and super-sampling visualization algorithms that greatly enhances the realism of 3-D reconstructions of the Visible Human data sets. Objects are classified on the basis of ellipsoidal regions in RGB space. The ellipsoids are used for super-sampling in the visualization process.

[New kinds of 3-dimensional atlases of the anatomy and function of the human body]. / Neuartige dreidimensionale Atlanten der Anatomie und Funktion des menschlichen Körpers.

It is a drawback of classical multimedia programs for the visualization of spatial knowledge, that they are based on a limited number of predefined views. This paper describes a model that combines pictorial and symbolic knowledge about spatial structures in a way that allows arbitrary views of the scene and the interrogation of the model in the context of the actual view. The style of the pictorial presentation only depends on the objective and the phantasy of the user. The functionality of the approach is demonstrated with the example of the human head. It is furthermore shown that the model potentially allows the simulation or generation of all classical visual teaching aids for anatomy.

A new representation of knowledge concerning human anatomy and function.

By integrating concepts of computer graphics and artificial intelligence, novel ways of representing medical knowledge become possible. They allow unprecedented possibilities ranging from three-dimensional interactive atlases to systems for surgery rehearsal.

Consideration of time-dose-patterns in 3D treatment planning. An approach towards 4D treatment planning.

PURPOSE: The rendering of the 3D dose distribution together with anatomical information and the volumes of interest (VoI) is essential to get a visual impression of the treatment plan and to find modifications for the optimization of the dose distribution. The integration of biological effects into the 3D treatment planning is of interest for the assessment of different time-dose patterns. MATERIALS AND METHODS: One way of taking into account biological data is to relate the physical dose in critical structures to the corresponding tolerance dose. For that purpose the applied time-dose pattern has to be converted into the standard fractionation scheme being the basis of the tolerance dose. Generally any model can be used for these calculations. Here a modified incomplete repair model is used to calculate the relative biological dose distribution (RBD). The visualization of these biologically isoeffective dose distributions can be performed in the same manner as the physical dose so that the physical and biological dose distributions can by displayed side by side. As this is equivalent to introducing the time as a fourth dimension into 3D treatment planning this is called 4D treatment planning. RESULTS: From 3D dose matrices the biologically isoeffective dose distributions are calculated for the organs at risk. The changes introduced by different time-dose patterns are displayed using the same technique as for rendering 3D treatment plans. The visualisation of the three-dimensional biological dose distributions is shown by means of a patient with an oesophagus carcinoma. The RBD related to the tolerance dose of the organs at risk is displayed for different time-dose fractionations. CONCLUSION: The RBD distribution on a 3D treatment plan can be displayed in the same mode as the physical dose distribution. This offers additionally valuable information in a 3D treatment planning process about the dose to critical organs and the influence of different time-dose patterns.

A new method for practicing exploration, dissection, and simulation with a complete computerized three-dimensional model of the brain and skull.

In current practice, anatomical atlases are based on a collection of planar images presented in a book or, recently, stored on digital media. We present a new kind of interactive true three-dimensional (3D) anatomical atlases based on a volume model derived from MRI and CT. The model has a two-layer structure. The lower level is a volume model with a set of semantic attributes connected to each voxel. The semantic attributes are assigned by an anatomist using a volume editor. THe upper level represents a set of relations between these attributes. Interactive visualization tools such as multiple surface display, preparation of transparent material and cutting are provided. It is shown that the combination of this model with advanced tools for volume visualization provides the 'look and feel' of real dissection. The system therefore represents a bridge between real dissection of a cadaver and textbooks and classical atlases of anatomy. First tests have shown that the atlas system may be used successfully for teaching anatomy, but also as a reference for radiologists or surgeons. The powerful underlying data structure potentially includes all classical visual teaching aids. As a replacement of classical atlases, however, spatial resolution has still to be improved.